Phase 1 Trial for SHR-4394: PSMA-Targeted ADC Shows Early Activity in Advanced Prostate Cancer

New results provide encouraging preliminary evidence of antitumor activity for SHR-4394, an investigational antibody-drug conjugate (ADC) targeting PSMA in metastatic castration-resistant prostate cancer (mCRPC).

The findings come from a first-in-human 1hase 1 study evaluating SHR-4394 as a standalone treatment. The drug is designed to recognize PSMA, a protein frequently expressed on prostate cancer cells, and deliver a cytotoxic payload directly to the tumor. Unlike PSMA-targeted radioligand therapies, SHR-4394 uses a chemotherapy-based payload rather than radioactive isotopes.

The study enrolled 53 patients whose disease had progressed after at least one novel hormonal therapy and who had previously failed, could not tolerate, or declined chemotherapy. SHR-4394 was investigated at different doses and treatment intervals to evaluate its safety, tolerability, and preliminary efficacy.

Among 42 evaluable patients with high PSMA expression (SUVmax ≥20), 40.5% achieved a confirmed PSA reduction of at least 50% (PSA50), while 14.3% achieved a reduction of at least 90% (PSA90).

Radiological responses were also observed, with 6 of 17 evaluable patients (35.3%) achieving confirmed objective tumor responses.

Safety findings revealed substantial hematological toxicity. Grade 3 or higher treatment-related adverse events occurred in 45.3% of patients, including decreased neutrophil counts (34.0%), white blood cell counts (26.4%), anemia (15.1%), and platelet counts (11.3%). Serious treatment-related adverse events occurred in 17.0% of patients, and two discontinued treatment because of toxicity.

No treatment-related deaths or dose-limiting toxicities were reported, and the maximum tolerated dose was not reached.

Although these findings suggest preliminary activity, the study remains an early-phase, non-randomized trial involving a relatively small population. PSA response results were reported specifically for evaluable patients with high PSMA expression, and data on response durability, progression-free survival, and overall survival are not yet available.

The frequency of severe hematological adverse events also highlights the need for further safety evaluation.

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